Design, synthesis and evaluation the bioactivities of novel 1,3-dimethyl-6-amino-1H-indazole derivatives as anticancer agents.

Indoleamine 2,3-dioxygenase (IDO1) is a heme-containing enzyme mainly responsible for the metabolism of tryptophan to kynurenine. To date, the IDO1 inhibitors have been developed intensively for the re-activation of the anticancer immune response. In this report, we designed, and synthesized novel 1,3-dimethyl-6-amino indazole derivatives as IDO1 inhibitors based on the structure of IDO1 active site. We further examined their anticancer activity on hypopharyngeal carcinoma cells (FaDu), squamous cell carcinoma of the oral tongue (YD-15), breast cancer cells (MCF7), and human dental pulp stem cells (HDPSC). Of them, compound N-(4-bromobenzyl)-1,3-dimethyl-1H-indazol-6-amine (7) remarkably suppressed IDO1 expression in a concentration - dependent manner. In addition, 7 was the most potential anticancer compound with inducing apoptosis activity as well as selectively activated extracellular signal-regulated kinases (ERK) in mitogen-activated protein kinase (MAPK) pathways on FaDu cells. Finally, compound 7 suppressed cell mobility in wound healing assay with the reduced expression of matrix metalloproteinase MMP9. Taken together, we believe that 7 is the most promising compound, which may be applied to treatment of hypopharyngeal carcinoma.

Computational Integral Imaging Reconstruction via Elemental Image Blending without Normalization.

This paper presents a novel computational integral imaging reconstruction (CIIR) method using elemental image blending to eliminate the normalization process in CIIR. Normalization is commonly used in CIIR to address uneven overlapping artifacts. By incorporating elemental image blending, we remove the normalization step in CIIR, leading to decreased memory consumption and computational time compared to those of existing techniques. We conducted a theoretical analysis of the impact of elemental image blending on a CIIR method using windowing techniques, and the results showed that the proposed method is superior to the standard CIIR method in terms of image quality. We also performed computer simulations and optical experiments to evaluate the proposed method. The experimental results showed that the proposed method enhances the image quality over that of the standard CIIR method, while also reducing memory usage and processing time.

Antitumor effects of valdecoxib on hypopharyngeal squamous carcinoma cells.

The antitumoral effects of valdecoxib (Val), an United States Food and Drug Administration-approved anti-inflammatory drug that was withdrawn due to the side effects of increased risk of cardiovascular adverse events, were investigated in hypopharyngeal squamous cell carcinoma cells by performing a cell viability assay, transwell assay, immunofluorescence imaging, and Western blotting. Val markedly inhibited cell viability with an IC50 of 67.3 µM after 48 h of treatment, and also downregulated cell cycle proteins such as Cdks and their regulatory cyclin units. Cell migration and invasion were severely suppressed by inhibiting integrin α4/FAK expression. In addition, Val activated the cell cycle checkpoint CHK2 in response to excessive DNA damage, which led to the activation of caspase-3/9 and induced caspase-dependent apoptosis. Furthermore, the signaling cascades of the PI3K/AKT/mTOR and mitogen-activated protein kinase pathways were significantly inhibited by Val treatment. Taken together, our results indicate that Val can be used for the treatment of hypopharyngeal squamous cell carcinoma.

Computational Three-Dimensional Imaging System via Diffraction Grating Imaging with Multiple Wavelengths.

This paper describes a computational 3-D imaging system based on diffraction grating imaging with laser sources of multiple wavelengths. It was proven that a diffraction grating imaging system works well as a 3-D imaging system in our previous studies. The diffraction grating imaging system has advantages such as no spherical aberration and a low-cost system, compared with the well-known 3-D imaging systems based on a lens array or a camera array. However, a diffraction grating imaging system still suffers from noises, artifacts, and blurring due to the diffraction nature and illumination of single wavelength lasers. In this paper, we propose a diffraction grating imaging system with multiple wavelengths to overcome these problems. The proposed imaging system can produce multiple volumes through multiple laser illuminators with different wavelengths. Integration of these volumes can reduce noises, artifacts, and blurring in grating imaging since the original signals of 3-D objects inside these volumes are integrated by our computational reconstruction method. To apply the multiple wavelength system to a diffraction grating imaging system efficiently, we analyze the effects on the system parameters such as spatial periods and parallax angles for different wavelengths. A computational 3-D imaging system based on the analysis is proposed to enhance the image quality in diffraction grating imaging. Optical experiments with three-wavelength lasers are conducted to evaluate the proposed system. The results indicate that our diffraction grating imaging system is superior to the existing method.

Image Enhancement for Computational Integral Imaging Reconstruction via Four-Dimensional Image Structure.

This paper describes the image enhancement of a computational integral imaging reconstruction method via reconstructing a four-dimensional (4-D) image structure. A computational reconstruction method for high-resolution three-dimensional (3-D) images is highly required in 3-D applications such as 3-D visualization and 3-D object recognition. To improve the visual quality of reconstructed images, we introduce an adjustable parameter to produce a group of 3-D images from a single elemental image array. The adjustable parameter controls overlapping in back projection with a transformation of cropping and translating elemental images. It turns out that the new parameter is an independent parameter from the reconstruction position to reconstruct a 4-D image structure with four axes of x, y, z, and k. The 4-D image structure of the proposed method provides more visual information than existing methods. Computer simulations and optical experiments are carried out to show the feasibility of the proposed method. The results indicate that our method enhances the image quality of 3-D images by providing a 4-D image structure with the adjustable parameter.

Image Enhancement of Computational Reconstruction in Diffraction Grating Imaging Using Multiple Parallax Image Arrays.

This paper describes an image enhancement method of computational reconstruction for 3-D images with multiple parallax image arrays in diffraction grating imaging. A 3-D imaging system via a diffraction grating provides a parallax image array (PIA) which is a set of perspective images of 3-D objects. The parallax images obtained from diffraction grating imaging are free from optical aberrations such as spherical and chromatic aberrations that are always involved in the 3-D imaging via a lens array. The diffraction grating imaging system for 3-D imaging also can be made at a lower cost system than a camera array system. However, the parallax images suffer from the speckle noise due to a coherent source; also, the noise degrades image quality in 3-D imaging. To remedy this problem, we propose a 3-D computational reconstruction method based on multiple parallax image arrays which are acquired by moving a diffraction grating axially. The proposed method consists of a spatial filtering process for each PIA and an overlapping process. Additionally, we provide theoretical analyses through geometric and wave optics. Optical experiments are conducted to evaluate our method. The experimental results indicate that the proposed method is superior to the existing method in 3-D imaging using a diffraction grating.

Computational reconstruction for three-dimensional imaging via a diffraction grating.

This paper describes a computational reconstruction method for 3-D imaging via a diffraction grating. An optical device consisting of a diffraction grating with a camera produces a parallax image array (PIA) for 3-D imaging in an efficient way according to recent researches. Unlike other capturing systems for a PIA such as a lens array with a camera and a camera array, a diffraction grating with a camera has an advantage in terms of the optical system complexity. However, since the diffraction grating is transparent, the captured raw image by the diffraction grating has no feature to detect the boundary of each parallax image. Moreover, the diffraction grating allows parallax images to overlap each other due to its optical property. Those problems prevent computational reconstruction from generating 3-D images. To remedy those problems, we propose a 3-D computational reconstruction method via a diffraction grating. The proposed method using a diffraction grating includes analyzing the PIA pickup process and converting a captured raw image into a well-defined PIA. Our analysis introduces a virtual pinhole; thus, a diffraction grating works as a camera array. Also, it defines the effective object area to segment parallax images and provides a mapping between each segmented parallax image and corresponding virtual pinhole. The minimum image area is also defined to determine the minimum field of view for our reconstruction. Optical experimental results indicated the proposed theoretical analysis and computational reconstruction in diffraction grating imaging are feasible in 3-D imaging. To our best knowledge, this is the first report on 3-D computational reconstruction via a diffraction grating.

Different Cellular Effects of Platinum Nanoparticles on RAW 264.7 Cells.

The cellular effects of platinum nanoparticle (PtNP) and platinum nanocolloid (PtNC) were investigated on murine leukemia Raw 264.7 cells. PtNP induced strong cytotoxic effects on Raw 264.7 cells while PtNC showed only mild cytotoxicity. Dramatic reduction in cell growth and morphological changes were observed for cells treated with PtNPs while PtNC did not show these effects. Both PtNPs and PtNC suppressed nitric oxide production, but PtNPs were superior to PtNC. PtNP strongly suppressed the expression of iNOS, COX-2 proteins and the phosphorylation of AKT on LPS-stimulated Raw 264.7 cells while PtNC showed only weak effects on these proteins. Our data showed that the preparation method of platinum nanoparticles may cause different cellular effects on cell growth and signaling.

Morphological Feature of Pluronic F127 and Its Application in Burn Treatment.

The morphological features of pluronic F127 at various concentrations were investigated and 20% aqueous pluronic F127 solution was chosen for the preparation of biomembrane. The pluronic solution was mixed with appropriate concentration of excipients such as PVA, Povidon S630, PG, Nipagin, Neomycin and Panthenol. The prepared pluronic F127 was thermosensitive, a liquid phase at low temperatures (≤10 °C) but converting into gel at temperatures above 20 °C, and formed stable biomembrane at 37 °C. The neomycin impregnated pluronic membrane suppressed the bacterial growth on agar plate by the sustained release of neomycin. The histological images of skin tissue after applying pluronic gel to burn injured area on rabbit confirmed that the pluronic F127 formulation functioned as a matrix to release drug as well as a biomembrane to protect burn injury. Thus, the formulated pluronic F127 may have a potential for the application of local treatment on burn injury.

Platinum Nanoparticles Induce Apoptosis on Raw 264.7 Macrophage Cells.

The cellular effects of platinum nanoparticles (PNP05, average size of 5 nm, and PNP30, average size of 30 nm) were investigated on murine leukemia Raw 264.7 cells. Cells treated with various concentrations of PNPs showed size-dependent cytotoxicity in an MTT assay with PNP5 of smaller nanoparticles higher toxicity than PNP30. Investigations on cell morphology, Annexin V assay, DNA fragmentation and the activity of caspase-3/-7 showed that PNPs induced apoptosis on Raw 264.7 cells by changing cell morphology and density, increasing cell population in apoptosis and causing nucleus fragmentation. Further study on caspase activity by Western blotting revealed that the apoptosis was induced by the activation of caspase-3 and -7. In addition, PNPs inactivated DNA repair system, generating dose-dependent DNA ladder bands on agarose gel electrophoresis. Taken together, PNPs triggered cytotoxicity on Raw 264.7 cells by suppressing cell growth/survival and inducing apoptosis.

Fisetin induces Sirt1 expression while inhibiting early adipogenesis in 3T3-L1 cells.

Fisetin (3,7,3',4'-tetrahydroxyflavone) is a naturally found flavonol in many fruits and vegetables and is known to have anti-aging, anti-cancer and anti-viral effects. However, the effects of fisetin on early adipocyte differentiation and the epigenetic regulator controlling adipogenic transcription factors remain unclear. Here, we show that fisetin inhibits lipid accumulation and suppresses the expression of PPARγ in 3T3-L1 cells. Fisetin suppressed early stages of preadipocyte differentiation, and induced expression of Sirt1. Depletion of Sirt1 abolished the inhibitory effects of fisetin on intracellular lipid accumulation and on PPARγ expression. Mechanistically, fisetin facilitated Sirt1-mediated deacetylation of PPARγ and FoxO1, and enhanced the association of Sirt1 with the PPARγ promoter, leading to suppression of PPARγ transcriptional activity, thereby repressing adipogenesis. Lowering Sirt1 levels reversed the effects of fisetin on deacetylation of PPARγ and increased PPARγ transactivation. Collectively, our results suggest the effects of fisetin in increasing Sirt1 expression and in epigenetic control of early adipogenesis.

Polyfluorinated substances in abiotic standard reference materials.

The National Institute of Standards and Technology (NIST) has a wide range of Standard Reference Materials (SRMs) which have values assigned for legacy organic pollutants and toxic elements. Existing SRMs serve as homogenous materials that can be used for method development, method validation, and measurement for contaminants that are now of concern. NIST and multiple groups have been measuring the mass fraction of a group of emerging contaminants, polyfluorinated substances (PFASs), in a variety of SRMs. Here we report levels determined in an interlaboratory comparison of up to 23 PFASs determined in five SRMs: sediment (SRMs 1941b and 1944), house dust (SRM 2585), soil (SRM 2586), and sludge (SRM 2781). Measurements presented show an array of PFASs, with perfluorooctane sulfonate being the most frequently detected. SRMs 1941b, 1944, and 2586 had relatively low concentrations of most PFASs measured while 23 PFASs were at detectable levels in SRM 2585 and most of the PFASs measured were at detectable levels in SRM 2781. The measurements made in this study were used to add values to the Certificates of Analysis for SRMs 2585 and 2781.

Preparation and Biophysical Characterization of Poly(amidoamine) Dendrimer-Poly(acrylic acid) Graft.

A series of PAMAM dendrimer generation 5-poly(acrylic acid) grafts were prepared to evaluate the potential use of dendritic grafts as a drug encapsulated nanocarrier. The structural features of the synthesized polymer graft were identified by FT-IR and 1H-NMR spectra and the biophysical properties were characterized by measuring its particle size and zeta potential. The prepared dendrimer G5-PAA grafts had particle size in the range of 600 to 900 nm and the size increased proportionally with the number of PAA on dendrimer surface. The electrostatic property of the dendrimer G5-PAA, carried out by HPLC reversed phase column analysis and the measurement of zeta potential, revealed that both migration time and zeta potential were dependent on the number of grafted PAA. The number of free amino groups on dendrimer G5-PAA, determined quantitatively by fluorescamine assay, was in a reverse order with the reaction mole ratio of dendrimer to PAA. In addition, dendrimer G5-PAA showed a pH-dependent solubility in aqueous solution with characteristic pH region of solubility, depending on the dendrimer generation. The observed biophysical properties indicate that PAMAM dendrimer G5-PAA is promising as a drug encapsulated nanocarrier.

Antioxidative Activity of Platinum Nanocolloid and Its Protective Effect Against Chemical-Induced Hepatic Cellular Damage.

Oxidative stress, a major cause of cellular injuries, is closely associated with a variety of chronic diseases such as cancer, liver diseases, degenerative brain disease and aging. In this study, we investigated antioxidant properties of platinum nanocolloid (PNC) against various oxidative stress conditions in vitro/in vivo by treating PNC on liver cell or tissue. Antioxidant activities of the PNC were determined by measuring quenching capacity on reactive oxygen species and its protective action against hydrogen peroxide or CCl4-induced oxidative cellular damage in HepG2 cell or liver tissue of mice. In vitro study, PNC markedly suppressed the production H2O2, ·OH, α,α-diphenyl-ß-picrylhydrazyl radical and nitric oxide in a dose-dependent manner. PNC also inhibited hydrogen peroxide-induced oxidative cellular damage in HepG2 hepatocytes. In vivo study with mice, PNC reduced hepatic lipid peroxidation and CCl4 induced toxicity. Our results support that platinum nanocolloid has antioxidant activities and protects hepatic cellular oxidative damage. Thus platinum nanocolloid may have a potential to be used as an antioxidant supplement.

Axially moving a lenslet array for high-resolution 3D images in computational integral imaging.

This paper presents a new high-resolution computational integral imaging system employing a pickup with the axial movement of a lenslet array and a computation reconstruction algorithm with pixel-to-pixel mapping. In the proposed method, a lenslet array and its image sensor are moved together along the z-axis direction (or axial direction) and a series of elemental image arrays are obtained while moving. The elemental image arrays are then applied to pixel-to-pixel mapping without interpolation for the reconstruction of 3D slice images. Also, an analysis of the proposed reconstruction method is provided. To show the usefulness of the proposed method, experiments are conducted. The results indicate that the proposed method is superior to the existing method such as MALT in terms of image quality.

Three-dimensional imaging and visualization using off-axially distributed image sensing.

This Letter presents an off-axially distributed image sensing (ODIS) system for three-dimensional (3D) imaging and visualization. The off-axially distributed sensing method provides both lateral and longitudinal perspectives for 3D scenes even though the sensor moves along a slanted, one-dimensional path. A 3D volume is generated from a set of recorded images by use of a computational algorithm based on ray backprojection. Preliminary experimental results are presented to illustrate the feasibility of the proposed system. To the best of our knowledge, this is the first report on 3D imaging and visualization using ODIS.

Artifact analysis and image enhancement in three-dimensional computational integral imaging using smooth windowing technique.

We propose an artifact analysis in computational integral imaging and the image enhancement method based on the analysis using the smooth windowing technique. Blurring and lenslet artifacts, which are major problems in computational integral imaging, are defined and analyzed using a signal model. Applying a smooth and continuous window such as the triangular window to computational integral imaging reconstruction provides a dramatic improvement in terms of image quality. Experimental results are presented to show the validity of our method. To our best knowledge, this is the first trial to control a window function in computational integral imaging.

Quantitative determination of perfluorochemicals and fluorotelomer alcohols in plants from biosolid-amended fields using LC/MS/MS and GC/MS.

Analytical methods for determining perfluorochemicals (PFCs) and fluorotelomer alcohols (FTOHs) in plants using liquid chromatography/tandem mass spectrometry (LC/MS/MS) and gas chromatography/mass spectrometry (GC/MS) were developed, and applied to quantify a suite of analytes in plants from biosolid-amended fields. Dichloromethane-methanol and ethylacetate were chosen as extracting solutions for PFCs and FTOHs, respectively. Nine perfluorocarboxylic acids (PFCAs), three perfluorosulfonic acids (PFSAs), and ten FTOHs were monitored. Most PFCAs and perfluorooctanesulfonate (PFOS) were quantifiable in plants grown in contaminated soils, whereas PFCs went undetected in plants from two background fields. Perfluorooctanoic acid (PFOA) was a major homologue (∼10-200 ng/g dry wt), followed by perfluorodecanoic acid (∼3-170 ng/g). [PFOS] in plants (1-20 ng/g) generally was less than or equal to most [PFCAs]. The site-specific grass/soil accumulation factor (GSAF = [PFC](Grass)/[PFC](Soil)) was calculated to assess transfer potentials from soils. Perfluorohexanoic acid had the highest GSAF (= 3.8), but the GSAF decreased considerably with increasing PFCA chain length. Log-transformed GSAF was significantly correlated with the PFCA carbon-length (p < 0.05). Of the measured alcohols, 8:2nFTOH was the dominant species (≤1.5 ng/g), but generally was present at ≥10× lower concentrations than PFOA.

Image quality enhancement of computational integral imaging reconstruction for partially occluded objects using binary weighting mask on occlusion areas.

This paper presents an image quality enhancement of computational integral imaging reconstruction (CIIR) method by using a binary weighting mask on occlusion areas in elemental images. The proposed method utilizes a block-matching algorithm to estimate the occlusion areas in elemental images. Then, a binary weighting mask generated from the estimated occlusion area is applied to our CIIR method. This minimizes the overlapping effect of occluding objects in the reconstructed plane images and thus improves visual quality dramatically. To show the usefulness of our proposed scheme, we conduct several experiments and present the results. The experimental results indicate that our method is superior to the existing methods.